title: High mobility group box 1 (HMGB1) activates an autophagic response to oxidative stress.
abstract: OBJECTIVE
  Autophagy, the process by which cells break down spent biochemical and damaged components, plays an important role in cell survival following stress. High mobility group box 1 (HMGB1) regulates autophagy in response to oxidative stress.
  
  
  RESULTS
  Exogenous hydrogen peroxide (H(2)O(2)) treatment or knockdown of the major superoxide scavenger enzyme, superoxide dismutase 1 (SOD1), by small interfering RNA (siRNA) increases autophagy in mouse and human cell lines. Addition of either SOD1 siRNA or H(2)O(2) promotes cytosolic HMGB1 expression and extracellular release. Importantly, inhibition of HMGB1 release or loss of HMGB1 decreases the number of autophagolysosomes and autophagic flux under oxidative stress in vivo and in vitro.
  
  
  METHODS
  HMGB1 release may be a common mediator of response to oxidative stress.
  
  
  CONCLUSIONS
  HMGB1 is important for oxidative stress-mediated autophagy and serves as a new target for the treatment of stress-associated disorders.
authors.affiliation: Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh, PA 15213, USA. tangd2@upmc.edu
authors.forename: Daolin
authors.initials: D
authors.lastname: Tang
authors.forename: Rui
authors.initials: R
authors.lastname: Kang
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Livesey
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Zeh
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lotze
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005455:Fluorescent Antibody Technique; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D034622:RNA Interference; D014867:Water / Q000494:pharmacology
chemical_list: D024243:HMGB1 Protein; D014867:Water